Regenerative Medicine and Heart Transplantation Unit, Fundación para la Investigación Hospital La Fe, Valencia, Spain.
Stem Cells Dev. 2013 Feb 1;22(3):501-11. doi: 10.1089/scd.2012.0340. Epub 2012 Sep 14.
Mesenchymal stem cells (MSC) are effective in treating myocardial infarction (MI) and previous reports demonstrated that hypoxia improves MSC self-renewal and therapeutics. Considering that hypoxia-inducible factor-1 alpha (HIF-1α) is a master regulator of the adaptative response to hypoxia, we hypothesized that HIF-1α overexpression in MSC could mimic some of the mechanisms triggered by hypoxia and increase their therapeutic potential without hypoxia stimulation. Transduction of MSC with HIF-1α lentivirus vectors (MSC-HIF) resulted in increased cell adhesion and migration, and activation of target genes coding for paracrine factors. When MSC-HIF were intramyocardially injected in infarcted nude rats, significant improvement was found (after treatment of infarcted rats with MSC-HIF) in terms of cardiac function, angiogenesis, cardiomyocyte proliferation, and reduction of fibrotic tissue with no induction of cardiac hypertrophy. This finding provides evidences for a crucial role of HIF-1α on MSC biology and suggests the stabilization of HIF-1α as a novel strategy for cellular therapies.
间充质干细胞（MSC）在治疗心肌梗死（MI）方面非常有效，先前的研究报告表明，缺氧可改善 MSC 的自我更新和治疗效果。鉴于缺氧诱导因子-1α（HIF-1α）是对缺氧适应反应的主要调节因子，我们假设 MSC 中的 HIF-1α过表达可以模拟缺氧引发的一些机制，并在没有缺氧刺激的情况下增加其治疗潜力。用 HIF-1α慢病毒载体（MSC-HIF）转导 MSC 可增加细胞黏附和迁移，并激活编码旁分泌因子的靶基因。当将 MSC-HIF 经心内注射到梗死裸鼠中时，发现心脏功能、血管生成、心肌细胞增殖和纤维化组织减少方面有显著改善（用 MSC-HIF 治疗梗死大鼠后），而没有诱导心肌肥厚。这一发现为 HIF-1α对 MSC 生物学的关键作用提供了证据，并提示稳定 HIF-1α 可作为细胞治疗的一种新策略。
